Itching is a sensation (pruritic sensation), which takes place at the cortex of the skin and the mucosa adjacent to the skin. The pruritic sensation is a sensation, which senses a parasite and an irritant of the skin cortex and removes an invading substance and an irritant by a scratching operation. Itching is a sensation, which can be easily understood as a sensation causing an impulse to scratch, but its mechanism has not been elucidated completely.
Diseases associated with itching are roughly classified into pruritic dermatitis associated with skin lesion (for example, atopic dermatitis, urticaria, psoriasis, xeroderma and trichophytia) and pruritus cutaneous which is not associated with skin lesion and provokes itching due to kidney dialysis and internal diseases [for example, diabetes, blood disease, cholestatic hepatitis (primary biliary liver cirrhosis) and kidney disease], hyperthyroidism and multiple sclerosis. In addition, the disease associated with severe itching includes diseases of cornea and conjunctiva, for example, allergic conjunctivitis. Recently, all diseases have rapidly increased to constitute a large problem in view of QOL (quality of life). Most itching diseases are common in the fact that vicious circle is caused by injure due to scratching. Histamine is known as a typical itching-producing substance and provokes itching in case it is externally added and is internally isolated from mastocytes.
An antihistaminic agent, an antiallergic agent and a steroid external agent are used for the treatment of pruritic dermatitis. However, all of them are not satisfactory medicaments for the treatment of itching due to pruritic dermatitis. Also it has recently been reported that elements other than histamine take part in itching due to atopic dermatitis. In many clinical cases, the antihistaminic agent and the antiallergic agent do not actually exert a remarkable effect on itching due to atopic dermatitis. In the treatment of pruritus cutaneous, the antihistaminic agent or the steroid external agent is employed sometimes, however, they do not exert any effect, and thus an effective therapy does not exist at present. As described above, there are no satisfactory medicaments for diseases associated with itching and it is required to develop a medicament, which effectively suppresses itching regardless of causative diseases from a clinical point of view.
The present inventors have found that a quinazoline derivative has a nociceptin antagonism and is useful as an analgesic (see Patent Document 1).
Patent Document 2 describes, as a compound having a carbonylamino group at the 2-position of the quinazoline skeleton, a quinazoline derivative that has a neuropeptide Y (NPY) receptor subtype Y5 inhibitory effect and is useful for pain relief and memory disorder. Patent Document 3 describes a quinazoline derivative, which is useful for bone diseases. Patent Document 4 describes a quinazoline derivative, which has a LTB4 (leucotriene B4) antagonism and is useful as an anti-inflammatory. However, these compounds have no guanidino group on the side chain at the 4-position of the quinazoline skeleton.    Patent Document 1: International Publication WO01/72710    Patent Document 2: International Publication WO97/20821    Patent Document 3: International Publication WO98/17267    Patent Document 4: International Publication WO98/38984